Diphenyl difluoroketone (EF-24) modulates dendritic cell responses. (101.30)

Abstract

Abstract Dendritic cells (DCs) are the most potent antigen-presenting cells that link the antigen-specific innate host responses with adaptive immunity. They recognize pathogens, pathogen-ligands and inflammatory signals via pattern recognition receptors. Inflammatory signals induce DC maturation and release of cytokines, chemokines and chemical mediators. We synthesized EF24, a known more potent analog of curcumin, and studied its immunomodulatory properties using immortalized murine DCs (JAWS II). We hypothesized that pharmacological downregulation of proinflammatory pathway by EF24 may suppress lipopolysaccharide (LPS)-induced phenotypic and functional changes in DCs. Murine bone marrow-derived JAWSII DCs were incubated with 1-10 µM EF24 with or without LPS (100 ng/ml). We investigated cell viability, morphology, expression of DC-specific markers and TLR4, NF-κB activity and cytokines. The short- and long-term treatment with EF24 suppressed the LPS-induced expression of DC-markers (CD80, CD86, MHC class II). Immunohistochemical expression of TLR4 in the cells was significantly reduced. Electrophoretic-mobility shift assay showed inhibition of LPS-induced NF-κB activation. EF24 also reduced the expression of IL-6, TNF-α and MCP-1 in DCs. There was no effect of EF24 on viability of DCs in the concentrations used. Overall, our results suggest that the immunomodulatory properties of EF24 may be of therapeutic value in inflammatory conditions, such as septic shock.